Combined pharmaco-EEG and pharmacopsychological study to estimate CNS effects of ketanserin in hypertensive patients.

When developing a new compound, potential side effects on the central nervous system (CNS) should be systematically investigated to determine the drug's safety, e.g., in respect of operating machinery or driving a car. The present study investigated CNS effects of ketanserin, a newly developed S2-serotonergic antagonist, in hypertensive patients. A multidimensional research strategy was used combining pharmaco-EEG and pharmacopsychological methods. The investigation consisted of two separate double-blind, randomized, and placebo-controlled studies, which were, however, planned together and in part included the same patients. The first study was carried out in 2 X 24 patients receiving chronic treatment with 2 X 20 mg ketanserin for 2 weeks, followed by 2 X 40 mg for a further 3 weeks. The second study was performed in 2 X 20 patients after subacute administration of 20 mg twice daily for six days. A multidimensional research strategy was employed to investigate CNS effects on functional and performance measures. Vigilance-related parameters, such as the alpha slow wave index and the absolute delta power, were assessed with pharmaco electroencephalography. Critical flicker-fusion frequency served as a measure of central sedation. Psychomotor performance and concentration tests were used to detect CNS effects which might impair car-driving ability. In addition, subjective well-being and adverse drug reactions were recorded. Ketanserin proved to be a safe drug to lower blood pressure. Only after chronic treatment were there slight indications that ketanserin could have a sedating and inhibiting action on the CNS. However, the differences between placebo and the ketanserin group, and the alterations within each group, were so minimal that they were not considered clinically relevant. A negative effect of ketanserin on car-driving ability is not very likely. The results show that the model was sensitive enough to detect CNS effects with sufficient certainty.